Preservation of organs

ABSTRACT

Apparatus and method of preserving life organs, the apparatus having an organ container in which the organ may be subjected to elevated pressure, a pump pulsatilely delivering perfusate into the organ and an oxygenator to oxygenate the perfusate effluent from the organ. A constant pressure bias maintains a minimum pressure on the perfusate between pulses. A fluid flow control system delivers driving fluid in a pulsed manner to the pump at a selected rate and at selected pulse duration. The method includes delivering pulsed oxygenated perfusate to the organ and uniformly conducting perfusate away from the organ and providing a constant pressure bias on the perfusate. Loss or gain of liquid volume caused by waste secretion by the organ is compensated for.

United States Patent [1 1 Theme et al.

[451 July 1, 1975 PRESERVATION OF ORGANS [73] Assignee: BaxterLaboratories, Inc., Morton Grove, Ill.

[22] Filed: Dec. 19, 1972 [21] Appl.No.: 316,612

Related US. Application Data [62] Division of Ser. No. 863,869, Oct. 6,1969, Pat. No.

[52] US. Cl 195/1.7; l95/1.7 [51] Int. Cl Cl2k 9/00 [58] Field of Search195/].7, 127; 23/2585 [56] References Cited UNITED STATES PATENTS 9/1971deRoissart l95/1.7 1/1972 Belzer et 195/1.7

Primary ExaminerRichard L. Huff Attorney, Agent, or FirmGarrettson Ellis5 7 ABSTRACT Apparatus and method of preserving life organs, theapparatus having an organ container in which the organ may be subjectedto elevated pressure, a pump pulsatilely delivering perfusate into theorgan and an oxygenator to oxygenate the perfusate effluent from theorgan. A constant pressure bias maintains a minimum pressure on theperfusate between pulses. A fluid flow control system delivers drivingfluid in a pulsed manner to the pump at a selected rate and at selectedpulse duration. The method includes delivering pulsed oxygenatedperfusate to the organ and uniformly conducting perfusate away from theorgan and providing a constant pressure bias on the perfusate. Loss orgain of liquid volume caused by waste secretion by the organ iscompensated for.

6 Claims, 4 Drawing Figures SHEET WJUU 6 cam on www JK Na 1 raEsEavArroNor ORGANS This application is a division of application Ser. No.863,869, filed Oct. 6, 1969, now US. Pat. No. 3,738,9i4.

BACKGROUND Field of the Invention The present invention relates totreatment of organs and more particularly to the clinical and laboratorypreservation and perfusion of life organs.

BRIEF SUMMARY OF THE INVENTION The present invention is directed to animproved method of artificially perfusing a life organ and includes thedelivery of perfusate to the organ with pulsatile pressure whileimposing a minimum pressure bias on the delivered perfusate betweenpressure pulses. This increases perfusate circulation through the organbetween pulses as well as during the pulses.

BRIEF DESCRIPTION OF THE FIGURES FIG. l is a schematic representation ofone presently preferred system according to the present invention;

FIGS. 2 and 3 are schematic circuit diagrams, each illustrating apresently preferred control unit which may respectively comprise part ofthe system of FIG. 1; and

PEG. 4 is a. schematic circuit diagram of another presently preferredcontrol unit which may also be used in the system of FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1

Referring now to FIG. 1, the organ preservation system, generallydesignated 20, is powered by a pneumatic source 22 which is preferablycompressed oxygen. If desired, conventional laboratory suppliedpneumatic source capable of generating pressures on the order of aboutto 25 p.s.i. could be used. The compressed oxygen is communicatedthrough line 24 to a control unit generally designated 26. The controlunit 26 has a plurality of dials 28, 34 and 36 and gauges 30 and 31which accommodate selective adjustment and monitoring of the compressedoxygen communicated through the line 24. Also, the control unit 26pulses the input oxygen and communicates the pulsed oxygen to the output32 of the unit 26. Significantly, dials 34 and 36 may be used to controlthe pulse rate and period of systole, respectively. of the output of thecontrol unit. An on-off switch 27 and gauge switches 134 and 138 arealso provided. A more detailed discussion of the structure and operationof the control unit 26 will be subsequently more fully described inconnection with FIG. 2.

The pulsed output pressure, termed systolic pressure, from the controlunit 26 is communicated through line 38 to a pump 41). One suitableembodiment of the pump 49 includes a cylindrical flexible pump bladder(not shown) fitted with silicone rubber tricuspid type check valves (notshown) in both ends to insure flow only in the desired direction. Therigid pump housing 46 encloses the bladder and seals the bladder at bothends, the pulsating pneumatic pressures from the control unit 26 beingcommunicated between the pump bladder and the interior of the pumphousing 46.

Perfusate, such as whole blood, disposed within the bladder of the pump40, is communicated through the conduit 42 to the simulated aorta 44with each high pressure pulse through the line 38. The simulated aorta44 is a perfusate or blood-receiving chamber and has a tubular siliconebladder (not shown) enclosed in a rigid cylindrical housing 48. Theinterior of the cylindrical housing 48 is in communication with aconstant biasing pressure through line 50 which is, in turn, coupledwith the control unmir26. The pressure in line 50 has a pre-selectedmagnit ude which exerts a biasing force upon the blood in the aorta 44.The bias pressure is preferably selectively adjustable in a range ofabout 0 to 200 millimeters of mercury above ambient. Thus, the forwardbias pressure on the blood will serve as a minimum or diastolicpressure.

The blood forced through the aorta 44 by the pump 40 is communicatedthrough line 52 to a temperature bath 54. Although any suitabletemperature bath could be used, one suitable type includes a coil ofline 52 disposed within a constant temperature water bath.

Blood emitted from the temperature bath 54 is then communicated througha port 56 to the interior of an organ container 58. Organ container 58is preferably formed of transparent material such as, for example,acrylic plastic so that the organ (not shown) therein may be readilyvisually observed without disrupting the environment. The container 58is constructed so as to accommodate elevated internal pressures such ason the order of about three atmospheres (45 p.s.i.g.). Also, theinterior of the container 58 is preferably regulated in temperature withconventional heat exchange apparatus 238 (FIG. 4). Thus, the container58 secures an organ (not shown) in a selected temperature and pressureenvironment.

Preferably, a tube 60 is connected to the organ (not shown) so as toreceive excreted waste or by-products of the organ perfusion, such asurine or bile (when the organ is respectively kidney or liver). Thesecretions are conducted to an accumulator 62 where they are madeavailable for examination and/or laboratory testing. The secretions mayor may not be returned to the system as perfusate depending upon thepreservation requirements of the particular organ.

After the pulsed blood has been circulated through the organ, the bloodis then carried away from the organ through line 64 to an oxygenator 66.The oxygenator 66 may be of any suitable conventional type, for example,a membrane oxygenator. Fresh oxygen is communicated to the oxygenator 66through line 68 from the control unit 26. In the oxygenator 66, carbondioxide in the blood is exchanged for oxygen, carbon dioxide rich fluidbeing communicated away from the oxygenator 66 through line 70 to thecontrol unit 26.

The oxygenated blood effluent from the oxygenator 66 is conducted byline 72 to simulated atrium 74. Significantly, an additional supply ofblood or other perfusate is also in communication with the atrium 74through line 76. The supply is maintained in a reservoir 78 tocompensate for any reduction in blood volume in the system resultingfrom secretion of fluids through the line 60 to the accumulator 62.Also, it should be appreciated that the container 58 is disposed at agreater vertical height than the oxygenator 66 and the oxygenator 66 is,in turn, disposed at a greater height than the atrium 74. Thus, the flowof blood from the organ in the container 58 through the oxygenator 66and to the atrium 74 is gravity flow.

Atrium 74 is a flexible silicone rubber receiver or chamber forreceiving the blood or other perfusate from the oxygenator 66 and thereservoir 78. Atrium 74 carries a substantial supply of blood and,therefore, ensures a non-interrupted venous inflow of blood to the pump40 and also provides a relatively uniform pres- I sure head for passivefilling of the pump 40. Thus, the atrium 74 cooperates with the pump 40to closely simulate natural physiologic conditions.

Briefly summarizing the method of preserving an organ in the container58, the system is primed with perfusate such as whole blood and purgedof all air or gas in the blood circulatory system. Pneumatic pressure,such as compressed oxygen, is pulsed by the control unit 26 which, inturn, actuates the pump 40 forcing blood into the aorta 44 and,thereafter, through the temperature control bath 54 into the organ (notshown). A bias pressure on the aorta 44 regulated through the controlunit 26 ensures a minimum diastolic pressure in the system.

Any liquid waste or like product created by the organ in the container58 during perfusion and preservation is delivered by the organ secretionducts to the tube 60 which conducts the secretion to the accumulator 62.The secretion is then readily available for examination and/orlaboratory testing or it may be returned to the system as perfusate. Aperfusate reservoir 78 regulates and maintains a fixed volume of bloodwithin the system and thus compensates any fluid removed through thetube 60 as a secretion.

A pressure head is developed at the oxygenator 66 and the atrium 74 bylocating the organ container 58 at a greater vertical height than theoxygenator 66, oxygenator 66 being in turn at a greater vertical heightthan atrium 74. The developed pressure head is sufficient to drive theblood through the oxygenator 66. Also, the control system 26 is manuallyset to regulate and control the rate of oxygenation as required by theorgan.

The oxygenated blood entering the atrium 74 is made available to thepump 40 in a continuous uninterrupted manner so that the pump 40 may beefficiently filled with blood when the pneumatic line 38 is vented toambient pressure, as between succesive systolic pressure pulses. Whenthe pneumatic line 38 is vented to ambient pressure, the pressure headin the atrium 74 opens the upper pump valve (not shown) and allows thepump to be refilled preparatory to initiation of another cycle ofpumping.

The Control Unit Embodiment of FIG. 2

Referring to FIG. 2, the control unit 26 comprises a pressure source 22which, as above described, may be compressed oxygen. It is presentlypreferred that the pressure from source 22 enter the control unit 26 atabout p.s.i.g. (pounds per square inch gauge). The pressure from thesource 22 is communicated through line 90 to an oscillator circuit 92.Oscillator circuit 92 has an or/nor gate 94 one side of which is incommunication with lines 90. The other side of the or/nor gate 94 is incommunication through line 96 with a pneumatic capacitor 98. A needlevalve 100 controls the flow of fluid from the capacitor 98 to a fixedresistor 102 and also to or/nor gate 104.

The regulated pressure supplied to the gate 94 passes freely through thegate until sufficient control pressure builds up in the capacitor 98 toswitch the gate 94 off. When the gate 94 is off. the capacitor 98discharges through the needle valve and vents through the restrictor102. When the pressure in pneumatic capacitor 98 reaches a predeterminedminimum level, the gate 94 switches on again to conduct the 20 p.s.i.g.pressure through line 96 to again allow the pressure to build up in thecapacitor 98. During the period when the gate is off the 20 p.s.i.g.pressure is conducted through line 106 to the gate 104. Thus, 20p.s.i.g. pressure is alternately conducted to the gate 104 and ventedthrough the resistor 102. The rate of alternation is termed the pulserate" and the pulse rate is determined by the setting on the needlevalve 100, needle valve 100 controlling the rate of charge and dischargeof the capacitor 98. The needle valve 100 may be manually set by turningknob 34 (FIG. 1).

A pressure regulator 108 reduces the 20 p.s.i.g. input pressure to 10p.s.i.g. and thereafter conducts the reduced pressure through line 1 10to the gate 104. A high pressure pulse in the line 106 switches the gate104 to the on position so that the 10 p.s.i.g. pressure through line 110 is conducted through line 112 as a pulse to the switching valve orfluid valve 116.

Fluid valve 116 responds to the pressure pulse from gate 104 by openingcommunication between line 118 and the output 32 of the control unit 26(see also FIG. 1). Line 118 communicates pressure from the source 22, aregulator 120 being interposed into the line to accommodate selectiveregulation of the pressure to the pump 40 (FIG. 1).

When gate 104 is switched off, i.e., when the oscillator 92. ventsthrough the fixed resistor 102, the fluid valve 116 will be operated tovent the increased pressure developed in the pump 40. Fluid valve 116 isbiased toward the vent position by fluid pressure existing in line 122.A pressure regulator 124 is disposed in the line 122 and controls theamount of pressure delivered to the right side of the fluid valve 116.Thus, the setting on regulator 120 determines the pressure which isnecessary to move the valve 116 from the extreme left position to theextreme right position to communicate driving fluid pressure to theoutput 32. The time period during which driving fluid is communicatedthrough the output 32 is increased by increasing the pressure setting onthe regulator 124. Hence, regulator 124 determines the period orduration of the systolic pressure.

A pneumatic capacitor 126 is interposed between the regulator 124 andthe pressure source 22 to dampen minor fluctuations in the pressure linecaused by the oscillator circuit 92.

Fluid pressure from the source 22 is communicated through line 1128 tothe aorta 44 (FIG. 1) as above described. A regulator 130 controlled byknob 28 (FIG. I) is disposed in the line 128 and is adjustable to setthe bias fluid pressure in line 128 to a predetermined minimum diastolicpressure.

Pressure gauge 30 is coupled to a switch 134 (see also FIG. 1) disposedin line 136. When switch 134 is in one position, the driving pressure tothe pump 40 is registered on the gauge 30. When the switch is placed inthe other position, the bias pressure to the aorta 44 is indicated onthe gauge 30. The other gauge 31 is coupled to a switch 138 which isdisposed in line 140. In one position the switch 138 causes the gauge 31to register the supply pressure from the pressure source 22 and, in theopposite position, causes gauge 31 to register the pressure on the rightside of fluid valve 116.

The Embodiment of FIG. 3

The control unit embodiment generally designated 144 and bestillustrated in FIG. 3 is, in many respects, substantially identical tothe control unit 26, like parts having like numerals throughout. Thecontrol unit 144 has a fluid valve control subsystem generallydesignated 149 and including a fluid valve 146 which is biased by spring148 toward the vent position. Thus, in the absence of a high pressuresystolic pulse at the lefthand side of the fluid valve 146, the pump 40(FIG. 1) will be vented through the valve 146. The spring biaseliminates the requirement for a regulated fluid pressure source toswitch the fluid valve to vent (i.e., to terminate the systole output).

The period of systole output is controlled by the or/- nor gates 150 and152 and the needle valve 154 as will now be described. The pulse signalsof the oscillator 92 switch the gate 150 to the on condition, causingfluid in line 156 to be conducted through the gate 150 and throughrestrictor 158 to the input 160 of gate 152. It should be observed thatthe fluid in line 156 is communicated from a pneumatic capacitor 162which is, in turn, connected to input line 164. Capacitor 162 provides amore constant pressure to the oscillator circuit 92. Input line 164 isin communication with the fluid supply 22 when switch 166 is in theillustrated on position. Switch 166 permits regulation of the supplypressure prior to placing the control unit 144 in the on condition. Thepressure regulation is accommodated by regulator 168. Fluid from thepressure source is initially filtered through filter 170 and, whenswitch 166 is in the illustrated closed position, the regulated fluidpressure is conducted through line .164 to the capacitor 162 and madeavailable to the gate 150.

When gate 150 is in the on condition, as above described, a pressurepulse will appear at gate 152 switching gate 152 to the on condition.Thus, the gate 150 isolates the systole control subsystem 149 from theoscillator circuit 92.

When gate 152 is in the on condition, the fluid in line 156 iscommunicated through line 172 to the left-hand side of fluid vaive 146causing the valve to communicate the fluid pressure in line 118 to thepump at output 32 (see FIG. 1). Significantly, the amount of pressurerequired to place gate 152 in the on condition is governed by the needlevalve 154. Thus, the needle valve 154 is adjusted to regulate the periodof systolic output of the fluid valve 146. When gate 152 is againswitched to the off condition, the spring 148 will return the fluidvalve 146 to the vent position, fluid in the left-hand side of the valve146 being vented through restrictor 174.

It should be appreciated in the control unit 144 that the gauge 31 andthe switch 138 are connected so that in one position gauge 31 monitorsthe pressure as regulated prior to placing the switch 166 in the oncondition and, in the opposite position, monitors the pressure assupplied to the oscillator circuit. The control unit 144 has theadvantage of more positive control of the switching action of the fluidvalve 146.

The Control Unit Embodiment of FIG. 4

The control unit illustrated in FIG. 4 and generally designated 180 issimilar to the control units 26 and 144 above described, like partshaving like numerals throughout. The control unit 180 differs in that itprovides a parallel circuit operating and controlling two fluidic pumpssimultaneously Also, the unit 180 is constructed for operation underhyperbaric conditions.

Most of the components of the control unit 180 are carried within ahyperbaric chamber 182 which may be formed of acryllic plastic and whichis constructed so as to maintain a hyperbaric environment. The chamber182 also contains the organ container 56 (not shown in FIG. 4).

The unit 180 comprises an oscillator circuit 184 which is substantiallysimilar to the oscillator circuit 92 above described, circuit 184comprising a gate 94, a fluidic capacitor 98 and a needle valve 100. Thecontrol unit 180 differs from control unit 92 in that a restrictor 186is disposed between the line 106 and restrictor 102. Restrictor 186minimizes the volume of pneumatic fluid required by the unit 180 andallows the size of the capacitor 98 to be minimized. The operation ofoscillator 184 is essentially identical to the operation of oscillator92 above described.

The output of oscillator 184 in line 106 is simultaneously communicatedto each of two fluid valve control subsystems 149 which may besubstantially identical to the fluid valve control subsystem 149 abovedescribed and illustrated in FIG. 3. The subsystems 149 are connected inparallel and relate one with another with line 192 which equalizes thefluid pressure between gates and also with line 194 which communicatesfluid in line 156 to gates 152 simultaneously. Each of the fluid valves146 is connected to a separate pump 196 and 198.

With continued reference to FIG. 4, fluid from the source 22 iscommunicated through the filter to the regulator 168 as above described(FIG. 3). The system is operated when the switch 166 is moved from theoff positioin illustrated in FIG. 4 to the on position opposite theposition illustrated in FIG. 4. In the on position the oscillator 184 isenergized and a pulsatile signal is developed by the subcircuits 149 todrive the pumps 196 and 198. The input pressure through the regulator168 is also communicated through line 200 to switch 202 so that gauge204 measures the pressure communicated through line 206 to theoxygenator 66. A restrictor 208 dampens pressure fluctuation in the lineservicing the pressure gauge 204 protecting it from shock damage.

The pressure from the supply 22 is also conducted to regulators 210 and212 which control the pumping pressure to pumps 198 and 196respectively. A switch 214 is provided to selectively turn the pump 198on or off so that a single pump may be operated if desired. Also, switch216, in one position, allows the pressure available to pump 196 to beregistered on the gauge 218 and, in the opposite position, allows thepressure in pump 198 to be monitored on gauge 218.

Gauge 218 is connected to switch 220 which in the illustrated positionmonitors the pressure on the selected one of the pumps 198 or 196 and,in the opposite position, monitors the pressure to the aorta. Aregulator 222 controls the pressure supplied to the oxygenator 66 and aflow meter 224 monitors and controls the rate of flow to the oxygenator.Diodes 226 and 228 prevent application of negative pressure on the gauge218 to avoid damaging the gauge.

A regulator 230 sets and controls the pressure in the hyperbaric chamber182 and relief valve 232 functions as a safety valve to avoidoverpressurizing the chamber 182. The pressure in the chamber 182 ismonitored by a gauge 234 which is protected from pressure fluctuation bya restrictor 236.

If desired, as illustrated in FIG. 4, the hyperbaric chamber 182 may beprovided with a heat exchanger 238 to maintain a constant predeterminedtemperature within the chamber 182 and/or of the perfusate.

The operation of the control circuit 180 is substantially similar to theoperation of the control circuit 144 (FIG. 3) above. However, the unit180 simultaneously drives two pumps which may be connected to the sameor different organs. The system accommodates preservation of an organ ina manner closely approaching actual physiological conditions andaccommodates a wide variety of controls to achieve maximum preservationeffect.

The invention may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The presentembodiments are, therefore, to be considered in all respects asillustrative and not restrictive, the scope of the invention beingindicated by the appended claims rather than by the foregoingdescription, and all changes which come within the meaning and range ofequivalency of the claims are therefore to be embraced therein.

What is claimed and desired to be secured by United States LettersPatent is:

1. In a method of artificially perfusing a life organ which methodincludes delivery of perfusate to the organ the improvement of:

developing a pulsatile pressure in the perfusate delivered to the organand imposing a minimum pressure bias on the delivered perfusatecirculated through the organ between pressure pulses.

2. A method of articially preserving life organs, comprising the stepsof:

placing the organ into a container;

pulsatilely pumping perfusate into the organ, while maintaining aminimum pressure bias on the perfusate between pulses and conducting theperfusate uniformly from the organ;

oxygenating the perfusate drawn from the organ with an oxygenator; and

controlling the temperature and the pulse rate of the perfusateconducted to the organ.

3. In a method as defined in claim 2, wherein said placing stepcomprises subjecting the organ to elevated pressures within thecontainer.

4. In a method as defined in claim 2 wherein said oxygenating stepcomprises disposing the container at a greater elevation than theoxygenator and delivering the perfusate from the organ to the oxygenatorby force of gravity.

5. In a method as defined in claim 2 further comprising conducting organsecretions away from the organ out of the container.

6. In a method as defined in claim 5 further comprising compensating forthe volume of secretions conducted away from the organ by increasing thevolume of perfusate available to the organ.

1. IN A METHOD OF ARTIFICIALLY PERFUSING LIFE ORGAN WHICH METHODINCLUDES DELIVERY OF PERFUSATE TO THE ORGAN THE IMPROVEMENT OF:DEVELOPING A PULSATILE PRESSURE IN THE PERFUSATE DELIVERED TO THE ORGANAND IMPOSING A MINIMUM PRESSURE BIAS ON THE DELIVERED PERDUSATECIRCULATED THROUGH ON THE ORGAN BETWEEN PRESSURE PULSES.
 2. A method ofarticially preserving life organs, comprising the steps of: placing theorgan into a container; pulsatilely pumping perfusate into the organ,while maintaining a minimum pressure bias on the perfusate betweenpulses and conducting the perfusate uniformly from the organ;oxygenating the perfusate drawn from the organ with an oxygenator; andcontrolling the temperature and the pulse rate of the perfusateconducted to the organ.
 3. In a method as defined in claim 2, whereinsaid placing step comprises subjecting the organ to elevated pressureswithin the Container.
 4. In a method as defined in claim 2 wherein saidoxygenating step comprises disposing the container at a greaterelevation than the oxygenator and delivering the perfusate from theorgan to the oxygenator by force of gravity.
 5. In a method as definedin claim 2 further comprising conducting organ secretions away from theorgan out of the container.
 6. In a method as defined in claim 5 furthercomprising compensating for the volume of secretions conducted away fromthe organ by increasing the volume of perfusate available to the organ.